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CDK4 or CDK6 deletion in adult hematopoiesis
harboring floxed Cdk4 or Cdk6 alleles and deleted CDK4 or CDK6 in adult hematopoiesis. We ascribed most hematopoietic side effects to the role of CDK6 in ery- throid development, myeloid differentiation and hematopoietic stem cell activation.
Our results identify CDK6 inhibition as major determi-
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nant for anemia development. Cdk6D/D mice display low RBC counts, reduced hemoglobin and hematocrit levels. With the exception of an altered spleen size these find- ings mirror the situation in complete Cdk6-/- mice.6 Changes in erythroid cells are already present 3 weeks after CDK6 deletion. Cdk4D/D mice show reduced RBC,
BC
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Figure 3. CDK6 alters the composition of the hematopoietic stem and progenitor pool. Analysis was performed 3 weeks post final polyinosinic–polycytidylic acid (poly(I:C)) injection. (A) Gating and representative flow cytometry pseudocolour plots. Percentage of (B) Lin-Sca-1+c-Kit+ (LSK) and (C) hematopoietic stem cells (HSC) (CD150+CD48-CD135-CD34-LSK) per 2.5x106 bone marrow (BM) cells (Cdk4∆/∆; Cdk6∆/∆; Cdk4/6fl/fl, n≥5/genotype). (D) Representative gating of DAPI/Ki-67 cell cycle staining of CD150+CD48+LSK (Fraction B) cells (E) and quantification of % cells in G (DAPI-, Ki-67-), G (DAPI-, Ki-67+) or S/G /M (DAPI+, Ki-67+) cell cycle phase per
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2.5x106 BM cells (n=3 (Cdk4∆/∆); n=3 (Cdk6∆/∆); n=6 (Cdk4/6fl/fl)). All comparisons were done with one-way ANOVA followed by Bonferroni’s Multiple Comparison Test,
*P≤0.05, **P≤0.01, ***P≤0.001.
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haematologica | 2021; 106(10)
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